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1.
Zhonghua Gan Zang Bing Za Zhi ; 27(9): 668-672, 2019 Sep 20.
Artigo em Chinês | MEDLINE | ID: mdl-31594089

RESUMO

Objective: To analyze serum HBV-RNA levels in patients with chronic hepatitis B whose serum HBV-DNA has dropped to undetected levels after treatment with entecavir, and to explore the correlation between HBV-RNA level and liver biochemical parameters, which lay the research foundation for the clinical significance of new serological marker HBV-RNA. Methods: HBeAg negatively detected 107 cases with chronic hepatitis B whose serum HBV-DNA test results were lower than detection level for six consecutive months after receiving standard nucleoside therapy for more than 12 months were included. HBV-RNA level was detected by Perkin-Elmer reagent. HBV-DNA level was detected by Roche Cobas. Hitachi automatic biochemical analyzer was used to detect ALT and AST. Architect chemiluminescence analyzer was used to detect HBsAg, HBeAg, anti-HBe and anti-HBc. RStudio software was performed to analyze the correlation between HBV-RNA level and liver biochemical parameters. Logistic regression was used to analyze the independent factors influencing HBV-RNA level. Results: The positive detection rate of serum HBV-RNA in patients with chronic hepatitis B whose serum HBV-DNA had dropped to undetected levels after ETV treatment was 22.43%. HBsAg, ALT and AST levels in HBV-RNA positive group were slightly higher than HBV-RNA negative group, while anti-HBc levels were slightly higher in HBV-RNA negative group. There was no difference in the level of anti-HBe between the HBV-RNA negative and the positive group. Logistic regression analysis showed that anti-HBc was an independent factor influencing the level of HBV-RNA detection (P = 0.021). Conclusion: HBV-RNA can be detected in some patients with chronic hepatitis B whose serum HBV-DNA level has dropped to undetected levels after ETV treatment. Serum HBV-RNA only comes from the direct transcription of cccDNA, so it is better than HBV-DNA and HBsAg to reflect cccDNA level or activity. Anti-HBc, as an independent factor influencing the level of HBV-RNA, may be used in combination as a new marker to predict the efficacy of antiviral therapy.


Assuntos
Hepatite B Crônica/diagnóstico , RNA Viral/sangue , DNA Viral/sangue , Anticorpos Anti-Hepatite/sangue , Antígenos de Superfície da Hepatite B/sangue , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B , Hepatite B Crônica/sangue , Humanos
2.
Rev Soc Bras Med Trop ; 52: e20190302, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31618309

RESUMO

INTRODUCTION: Solid-organ transplant recipients are at risk of hepatitis E virus (HEV) infection. We analyzed the seroprevalence/risk factors of HEV in Croatian liver transplant recipients. METHODS: Two hundred forty-two serum samples were tested for HEV immunoglobuline IgG/IgM and HEV RNA. Sociodemographic data and risk factors were collected using a questionnaire. RESULTS: HEV IgG seroprevalence rate was 24.4%. Positive/equivocal HEV IgM were found in two patients. HEV RNA was not detected. Logistic regression showed that older age, female gender, rural area/farm, water well, and septic tank were associated with HEV seropositivity. CONCLUSIONS: This study revealed a high exposure rate to HEV in Croatian liver recipients.


Assuntos
Vírus da Hepatite E/imunologia , Hepatite E/epidemiologia , Transplante de Fígado/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Croácia/epidemiologia , Estudos Transversais , Feminino , Anticorpos Anti-Hepatite/sangue , Hepatite E/imunologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Fatores de Risco , Estudos Soroepidemiológicos , Fatores Socioeconômicos
3.
BMC Infect Dis ; 19(1): 675, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31362697

RESUMO

BACKGROUND: Hepatitis E virus (HEV) infection is now recognized as a major cause of acute hepatitis worldwide. HEV specific antibodies develop shortly after infection and are thought to confer protection. CASE PRESENTATION: We report an immunocompromised patient who developed chronic HEV infection despite the presence of high level antibodies. HEV infection was detected using RT-PCR upon diagnostic evaluation due to increased liver enzymes. Upon retrospective analysis of stored serum samples we found that the patient was HEV RNA positive since 7 months. Chronic HEV infection was successfully treated with ribavirin. CONCLUSIONS: In conclusion, the patient suffered from a chronic course of HEV infection, which was successfully treated with ribavirin. Our case underlines the importance of RT-PCR for HEV diagnostics in immunosuppressed patients and supports the notion that HEV antibodies do not confer universal protection. Counseling patients at risk for chronic HEV infection seems advisable. The role of the humoral and T-cell mediated immune response in cases of HEV reinfection deserves further study.


Assuntos
Hepatite E/etiologia , Hepatite Crônica/etiologia , Transplante de Rim/efeitos adversos , RNA Viral/sangue , Formação de Anticorpos , Antivirais/uso terapêutico , Ensaio de Imunoadsorção Enzimática , Anticorpos Anti-Hepatite/sangue , Anticorpos Anti-Hepatite/imunologia , Hepatite E/diagnóstico , Hepatite E/tratamento farmacológico , Hepatite Crônica/diagnóstico , Hepatite Crônica/tratamento farmacológico , Humanos , Hospedeiro Imunocomprometido , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Ribavirina/uso terapêutico
4.
BMC Public Health ; 19(1): 1038, 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31375104

RESUMO

BACKGROUND: Age cohort screening for hepatitis C virus (HCV) might be an effective strategy if the majority of undiagnosed cases are concentrated in a particular age group. The objective of this study was to determine HCV prevalence in different age cohorts of the general population in the Central European part of Russia and second, to assess feasibility of HCV antigen testing for community screening programs. METHODS: Sera from 2027 volunteers were tested for anti-HCV (Architect Anti-HCV, Abbott Laboratories). All anti-HCV reactive samples were confirmed in an immunoblot and tested for HCV Ag (ARCHITECT HCV Ag, Abbott Laboratories), HCV RNA and HCV viral load. RESULTS: Out of 31 individuals with anti-HCV reactive result, 22 (71%) were confirmed by immunoblot, six were false positives and three were indeterminate. Active infection was observed in 73% of anti-HCV confirmed positives. Five out of 16 individuals had low HCV-RNA levels (< 10,000 IU/mL) and one of those had a very low level (594 IU/mL). Agreement between HCV Ag and HCV RNA was 100%. Total anti-HCV and active HCV infection rates were 1.09% (22/2027) and 0.79% (16/2027), respectively. The peak rates were observed in people 60 years or older (anti-HCV: 2.84% [95% CI: 1.66-4.74%], 13/319; HCV RNA/HCV Ag: 2.23% [95% CI: 1.20-4.00%], 10/319). CONCLUSIONS: Overall HCV prevalence is low, except in people 60 years or older. The latter should be considered as a target group for HCV screening. The high agreement between HCV RNA and HCV Ag suggests the utility of HCV Ag testing to confirm active infection in screening programs.


Assuntos
Serviços de Saúde Comunitária , Hepatite C/epidemiologia , Programas de Rastreamento/métodos , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Hepacivirus/genética , Hepacivirus/imunologia , Hepacivirus/isolamento & purificação , Hepatite C/sangue , Antígenos da Hepatite C/sangue , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Prevalência , RNA Viral/sangue , Federação Russa/epidemiologia , Adulto Jovem
5.
BMC Infect Dis ; 19(1): 588, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31277590

RESUMO

BACKGROUND: HIV controllers (HICs) are a rare group of HIV-1-infected individuals able to naturally control viral replication. Several studies have identified the occurrence of HIV dual infections in seropositive individuals leading to disease progression. In HICs, however, dual infections with divergent outcomes in pathogenesis have been described. CASE PRESENTATION: Here, we present a case report of a HIC diagnosed in late 1999 who displayed stable CD4+ T cell levels and low plasmatic viral load across 12 years of follow-up. In early 2013, the patient started to present an increase in viral load, reaching a peak of 10,000 copies/ml in early 2014, followed by an oscillation of viremia at moderate levels in the following years. The genetic diversity of env proviral quasispecies from peripheral blood mononuclear cells (PBMCs) was studied by single genome amplification (SGA) at six timepoints across 2009-2017. Phylogenetic analyses of env sequences from 2009 and 2010 samples showed the presence of a single subtype B variant (called B1). Analyses of sequences from 2011 and after revealed an additional subtype B variant (called B2) and a subsequent dominance shift in the proviral quasispecies frequencies, with the B2 variant becoming the most frequent from 2014 onwards. Latent syphilis related to unprotected sexual intercourse was diagnosed a year before the first detection of B2, evidencing risk behavior and supporting the superinfection hypothesis. Immunologic analyses revealed an increase in CD8+ and CD4+ T cell immune activation following viremia increase and minor T cell subset alterations during follow-up. HIV-specific T cell responses remained low throughout the follow-up period. CONCLUSIONS: Altogether, these results show that loss of viremia control in the HIC was associated with superinfection. These data alert to the negative consequences of reinfection on HIV pathogenesis, even in patients with a long history of viremia control and an absence of disease progression, reinforcing the need for continued use of adequate prevention strategies.


Assuntos
Infecções por HIV/virologia , HIV-1/fisiologia , Superinfecção/virologia , Replicação Viral/fisiologia , Adulto , Fármacos Anti-HIV/uso terapêutico , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/virologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/virologia , Feminino , Seguimentos , Infecções por HIV/tratamento farmacológico , HIV-1/isolamento & purificação , HIV-1/patogenicidade , Antígenos HLA-B/genética , Humanos , Leucócitos Mononucleares/virologia , Masculino , Filogenia , RNA Viral/sangue , Sífilis/diagnóstico , Carga Viral , Viremia/tratamento farmacológico , Viremia/virologia
6.
BMC Infect Dis ; 19(1): 590, 2019 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-31277583

RESUMO

BACKGROUND: Transfusion-Transmitted Zika virus (TT-ZIKV) has become an emerging threat to world blood banks due to the fast spread of ZIKV epidemics and high rate of asymptomatic infections. For the risk assessment of ZIKV infection in blood products, relevant studies in blood donations or blood donors tested for ZIKV were collected and analyzed systematically. The overall prevalence of ZIKV infection were estimated through meta-analysis and potential risk factors were detected. The results will provide important clues for the protocol design of blood screening tests. METHODS: Relevant articles about the rate of ZIKV detected in blood samples were identified from PubMed, Scopus and Web Of Science using key terms search strategy until October 7, 2017. Eligible articles were screened following inclusion and exclusion criteria. Meta-analysis and subgroup analyses were performed by software R3.4.1. Overall postdonation and posttransfusion follow-ups were analyzed. RESULTS: Ten literatures (528,947 blood samples) were included for meta-analysis. The overall pooled prevalence of ZIKV (RNA and antibody) in blood donations was 1.02% (95%CI 0.36-1.99). The pooled prevalence of ZIKV RNA in blood donations was 0.85% (95%CI 0.21-1.88) less than the pooled prevalence of anti-ZIKV antibodies 1.61% (95%CI 0.03-5.21), however the difference was not statistically significant (p = 0.52). The prevalence varied significantly in different geographical regions (p < 0.001). Blood donations were more than two times likely to be infected by ZIKV in Zika epidemic period (1.37, 95%CI 0.91-1.91) than in non-epidemic period (0.61, 95%CI 0-2.55). The prevalence of anti-ZIKV antibodies (1.61, 95%CI 0.03-5.21) was almost twice as much as ZIKV nucleic acid detected in blood donations (0.85, 95%CI 0.21-1.88). However, statistically significant differences were not observed. A total of 122 ZIKV positive blood donors were followed, of which 48 (39%) reported symptoms postdonation, but none of the 13 followed recipients reported any clinical symptoms related to Zika infection posttransfusion. CONCLUSION: The pooled prevalence of Zika infection in blood donations was 1.02%. The prevalence varied greatly and reached to high-risk level in most of the situations. The results suggest that nucleic acid tests (NAT) for blood screening and pathogen reduction/inactivation technology (PRT) should be implemented in Zika-endemic areas and appropriate strategies should be designed according to different conditions. More studies are needed in the future to provide more evidence.


Assuntos
Doadores de Sangue/estatística & dados numéricos , Infecção por Zika virus , Zika virus , Anticorpos Antivirais/sangue , Humanos , Prevalência , RNA Viral/sangue , Zika virus/genética , Zika virus/imunologia , Infecção por Zika virus/sangue , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/epidemiologia
7.
BMC Infect Dis ; 19(1): 626, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31307403

RESUMO

BACKGROUND: In the United States Hepatitis C virus (HCV) viral clearance is estimated to range between 20 and 30%. The objective of this study was to estimate the frequency of HCV clearance and identify correlates of viral clearance among patients newly identified as HCV antibody positive in a large urban health system in Los Angeles, California. METHODS: We identified patients between November 2015 and September 2017 as part of a newly implemented HCV screening and linkage-to-care program at University of California Los Angeles (UCLA) Health System. All patients were eligible for screening, though there were additional efforts to screen patients born between 1945 and 1965. We reviewed Medical records to categorize anti-HCV antibody positive patients as having spontaneously cleared HCV infection (HCV RNA not detected) or not (HCV RNA detected). We excluded those with a prior history of anti-HCV positivity or history of HCV treatment. We compared differences between those with and without detectable HCV RNA using chi-square test, Fisher's exact test, and t-test as appropriate. We assessed factors associated with HCV clearance using logistic regression analysis. RESULTS: Among the 320 patients included in this study, 56% were male. Baby boomers (52-72 years of age) comprised the single largest age group (62%). We found spontaneous HCV clearance in 58% (n = 185). HCV viral clearance was slightly higher among women as compared to men (63% vs. 53%; p value = 0.07) and varied by race/ethnicity: clearance among Blacks/African Americans was 37% vs. 58% among whites (p value = 0.02). After adjusting for age, race/ethnicity, and sex we found that those diagnosed with chronic kidney disease had a tendency of decreased HCV viral clearance (adjusted OR = 0.34; 95% CI 0.14-1.03). CONCLUSION: Of those patients newly identified as anti-HCV positive, 58% had cleared HCV virus, while the rest showed evidence of active infection. In addition, we found that clearance varied by race/ethnicity and clinical characteristics.


Assuntos
Hepacivirus/isolamento & purificação , Hepatite C/diagnóstico , Adolescente , Adulto , Afro-Americanos , Idoso , California/epidemiologia , Grupo com Ancestrais do Continente Europeu , Feminino , Hepacivirus/genética , Hepatite C/epidemiologia , Hepatite C/etnologia , Anticorpos Anti-Hepatite C/sangue , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Remissão Espontânea , Insuficiência Renal Crônica/diagnóstico , Estudos Retrospectivos , Adulto Jovem
8.
Arch Virol ; 164(10): 2493-2504, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31346769

RESUMO

One of the pathological forms of chronic hepatitis C is occult HCV infection (OCI), in which there is no detectable HCV RNA in plasma specimens but HCV RNA is present in PBMCs and liver biopsy specimens. The aim of this study is to estimate the prevalence of OCI in HIV-positive people who are injection drug users (IDUs). From April 2015 to August 2018, 161 Iranian IDUs with HIV infection enrolled in the study. Viral RNA was extracted from plasma and PBMC samples of participants, and the presence of HCV RNA was examined using RT nested PCR with primers from two conserved regions (5´-UTR and NS5B). HCV genotyping was performed using RFLP and sequencing methods. Of the 161 patients, 134 (83.2%) were positive for anti-HCV antibodies. All 27 patients who were negative for anti-HCV were also negative for HCV RNA in plasma, but five of them (18.5%) were positive for HCV RNA in PBMCs. Importantly, 9 out of 50 patients (18.0%) who apparently had recovered from HCV infection (i.e., were anti-HCV positive and HCV RNA negative) were positive for HCV RNA in PBMCs. Overall, 18.1% of the patients who had no signs of previous HCV infection or had apparently recovered from the disease had OCI. The HCV genotypes of the cases with OCI were as follows: five patients (35.7%) were infected with subtype 1a, eight patients (57.1%) were infected with subtype 3a, and one patient (7.1%) was infected with genotype 4. Thus, it seems that the prevalence of OCI in HIV-positive IDUs is extremely significant in Iran and is likely to delay the global eradication of HCV infection until 2030.


Assuntos
Usuários de Drogas , Infecções por HIV/complicações , Hepatite C Crônica/epidemiologia , Hepatite C Crônica/patologia , RNA Viral/sangue , Abuso de Substâncias por Via Intravenosa/complicações , Adulto , Idoso , Feminino , Genótipo , Técnicas de Genotipagem , Hospitais Universitários , Humanos , Irã (Geográfico) , Leucócitos Mononucleares/virologia , Masculino , Pessoa de Meia-Idade , Plasma/virologia , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Prevalência , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adulto Jovem
9.
BMC Infect Dis ; 19(1): 601, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31291899

RESUMO

BACKGROUND: Despite effective antiretroviral therapy developed over the last decade, HIV infection remains a major worldwide public health problem. Recently, a promising preventive treatment has been made available for HIV prophylaxis, PrEP for pre-ExPosure Prophylaxis. Indeed, it was shown to significantly reduce the risk of HIV infection in patients exposed to high risk of infection such as men having sex with men (MSM), heterosexuals and people who inject drugs. Several issues pertaining to PrEP remain uncertain including short and long-term adverse events, drug resistance, risk compensation and resurgence of other sexually transmitted infections. CASE PRESENTATION: We report a case of a 52-year-old MSM eligible for PrEP as he was exposed to a high risk of HIV infection, presented no clinical symptoms of HIV primary infection and was seronegative for HIV. PrEP therapy was then initiated with fixed association of emtricitabine-tenofovir disoproxil. One month later, HIV tests using two different assays were positive, despite perfect compliance reported by the patient and confirmed by plasma drug level. A retrospective search for plasma viral RNA in the blood sample before PrEP initiation turned out positive. Genotyping and treatment sensitivity performed on sample after one month of PrEP showed a virus resistance to lamivudine and emtricitabine. Similar cases in the literature and pivotal studies have reported HIV infections in patients initiating or undergoing PrEP. These patients where either infected but still seronegative, displaying no clinical symptoms upon enrollment, or became infected during PrEP. Reasons are mainly poor compliance to treatment, resistance to PrEP, and lack of diagnosis before PrEP. Guidelines advocate safe sex behavior before initiation, search for clinical signs of HIV primary infection and two different serologic tests performed with one-month interval. DISCUSSION AND CONCLUSIONS: Our patient newly HIV infected received PrEP as he was still seronegative. Current recommendations fail to screen recently HIV infected, but still seronegative patients who are initiating PrEP. This issue raises strong concerns regarding the lack of adequate selection for eligibility to PrEP and may contribute to exposing partners to HIV infection and select viral mutations. Infection risk could be minimized by search for plasma viral HIV RNA at pre-inclusion, at least for patients suspected of unsafe behaviors such as non-respect of the non-exposure period before PrEP initiation.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/prevenção & controle , Guias de Prática Clínica como Assunto/normas , Profilaxia Pré-Exposição/normas , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/farmacologia , Farmacorresistência Viral/efeitos dos fármacos , Farmacorresistência Viral/genética , Infecções por HIV/sangue , Infecções por HIV/diagnóstico , Homossexualidade Masculina , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , RNA Viral/genética
10.
N Engl J Med ; 381(9): 803-815, 2019 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-31339677

RESUMO

BACKGROUND: Two drugs under consideration for inclusion in antiretroviral therapy (ART) regimens for human immunodeficiency virus (HIV) infection are dolutegravir (DTG) and tenofovir alafenamide fumarate (TAF). There are limited data on their use in low- and middle-income countries. METHODS: We conducted a 96-week, phase 3, investigator-led, open-label, randomized trial in South Africa, in which we compared a triple-therapy combination of emtricitabine (FTC) and DTG plus either of two tenofovir prodrugs - TAF (TAF-based group) or tenofovir disoproxil fumarate (TDF) (TDF-based group) - against the local standard-of-care regimen of TDF-FTC-efavirenz (standard-care group). Inclusion criteria included an age of 12 years or older, no receipt of ART in the previous 6 months, a creatinine clearance of more than 60 ml per minute (>80 ml per minute in patients younger than 19 years of age), and an HIV type 1 (HIV-1) RNA level of 500 copies or more per milliliter. The primary end point was the percentage of patients with a 48-week HIV-1 RNA level of less than 50 copies per milliliter (as determined with the Snapshot algorithm from the Food and Drug Administration; noninferiority margin, -10 percentage points). We report the primary (48-week) efficacy and safety data. RESULTS: A total of 1053 patients underwent randomization from February 2017 through May 2018. More than 99% of the patients were black, and 59% were female. The mean age was 32 years, and the mean CD4 count was 337 cells per cubic millimeter. At week 48, the percentage of patients with an HIV-1 RNA level of less than 50 copies per milliliter was 84% in the TAF-based group, 85% in the TDF-based group, and 79% in the standard-care group, findings that indicate that the DTG-containing regimens were noninferior to the standard-care regimen. The number of patients who discontinued the trial regimen was higher in the standard-care group than in the other two groups. In the per-protocol population, the standard-care regimen had equivalent potency to the other two regimens. The TAF-based regimen had less effect on bone density and renal function than the other regimens. Weight increase (both lean and fat mass) was greatest in the TAF-based group and among female patients (mean increase, 6.4 kg in the TAF-based group, 3.2 kg in the TDF-based group, and 1.7 kg in the standard-care group). No resistance to integrase inhibitors was identified in patients receiving the DTG-containing regimens. CONCLUSIONS: Treatment with DTG combined with either of two tenofovir prodrugs (TAF and TDF) showed noninferior efficacy to treatment with the standard-care regimen. There was significantly more weight gain with the DTG-containing regimens, especially in combination with TAF, than with the standard-care regimen. (ADVANCE ClinicalTrials.gov number, NCT03122262.).


Assuntos
Adenina/análogos & derivados , Antirretrovirais/administração & dosagem , Infecções por HIV/tratamento farmacológico , HIV-1 , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Ácidos Fosforosos/administração & dosagem , Adenina/administração & dosagem , Adenina/efeitos adversos , Adolescente , Adulto , Antirretrovirais/efeitos adversos , Densidade Óssea/efeitos dos fármacos , Contagem de Linfócito CD4 , Quimioterapia Combinada , Feminino , Inibidores de Integrase de HIV/administração & dosagem , HIV-1/genética , HIV-1/isolamento & purificação , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Ácidos Fosforosos/efeitos adversos , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Pró-Fármacos/administração & dosagem , RNA Viral/sangue , Uracila/administração & dosagem , Uracila/análogos & derivados , Carga Viral , Adulto Jovem
11.
N Engl J Med ; 381(9): 816-826, 2019 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-31339676

RESUMO

BACKGROUND: An efavirenz-based regimen (with a 600-mg dose of efavirenz, known as EFV600) was the World Health Organization preferred first-line treatment for human immunodeficiency virus type 1 (HIV-1) infection until June 2018. Given concerns about side effects, dolutegravir-based and low-dose efavirenz-based combinations have been considered as first-line treatments for HIV-1 in resource-limited settings. METHODS: We conducted an open-label, multicenter, randomized, phase 3 noninferiority trial in Cameroon. Adults with HIV-1 infection who had not received antiretroviral therapy and had an HIV-1 RNA level (viral load) of at least 1000 copies per milliliter were randomly assigned to receive either dolutegravir or the reference treatment of low-dose efavirenz (a 400-mg dose, known as EFV400), combined with tenofovir and lamivudine. The primary end point was the proportion of participants with a viral load of less than 50 copies per milliliter at week 48, on the basis of the Food and Drug Administration snapshot algorithm. The difference between treatment groups was calculated, and noninferiority was tested with a margin of 10 percentage points. RESULTS: A total of 613 participants received at least one dose of the assigned regimen. At week 48, a viral load of less than 50 copies per milliliter was observed in 231 of 310 participants (74.5%) in the dolutegravir group and in 209 of 303 participants (69.0%) in the EFV400 group, with a difference of 5.5 percentage points (95% confidence interval [CI], -1.6 to 12.7; P<0.001 for noninferiority). Among those with a baseline viral load of at least 100,000 copies per milliliter, a viral load of less than 50 copies per milliliter was observed in 137 of 207 participants (66.2%) in the dolutegravir group and in 123 of 200 participants (61.5%) in the EFV400 group, with a difference of 4.7 percentage points (95% CI, -4.6 to 14.0). Virologic failure (a viral load of >1000 copies per milliliter) was observed in 3 participants in the dolutegravir group (with none acquiring drug-resistance mutations) and in 16 participants in the EFV400 group. More weight gain was observed in the dolutegravir group than in the EFV400 group (median weight gain, 5.0 kg vs. 3.0 kg; incidence of obesity, 12.3% vs. 5.4%). CONCLUSIONS: In HIV-1-infected adults in Cameroon, a dolutegravir-based regimen was noninferior to an EFV400-based reference regimen with regard to viral suppression at week 48. Among participants who had a viral load of at least 100,000 copies per milliliter when antiretroviral therapy was initiated, fewer participants than expected had viral suppression. (Funded by Unitaid and the French National Agency for AIDS Research; NAMSAL ANRS 12313 ClinicalTrials.gov number, NCT02777229.).


Assuntos
Benzoxazinas/administração & dosagem , Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/efeitos adversos , HIV-1 , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Adulto , Benzoxazinas/efeitos adversos , Quimioterapia Combinada , Feminino , Inibidores de Integrase de HIV/uso terapêutico , HIV-1/genética , HIV-1/isolamento & purificação , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Humanos , Lamivudina/administração & dosagem , Masculino , Obesidade/induzido quimicamente , Gravidez , RNA Viral/sangue , Tenofovir/administração & dosagem , Carga Viral/efeitos dos fármacos , Ganho de Peso/efeitos dos fármacos
12.
BMC Infect Dis ; 19(1): 541, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31221098

RESUMO

BACKGROUND: Hepatitis E is a liver disease caused by a small RNA virus known as hepatitis E virus (HEV). Four major genotypes infect humans, of which genotype 1 and 2 (HEV-1, HEV-2) are endemic mainly in Asia and responsible for waterborne epidemics. HEV-3 and HEV-4 are widely distributed in pigs and can be transmitted to humans mainly by undercooked meat, and contact with pigs. HEV-3 is the main genotype in industrialised countries with moderate climate conditions and object of this debate. MAIN TEXT: Whereas an HEV-3 infection in healthy humans is mostly asymptomatic, HEV-3 can induce chronic infection in immunocompromised individuals and acute-on-chronic liver failure (ACLF) in patients with underlying liver diseases. The number of reported cases of HEV-infections in industrialised nations increased significantly in the last years. Since HEV-3 has been transmitted by blood transfusion to other humans, testing of blood donors has been introduced or introduction is being discussed in some industrialised countries. In this article we summarise the arguments in favour of testing all blood donations for HEV-3. CONCLUSION: The number of HEV infection in the population and the possibility of HEV transmission by blood transfusion are increasing. Transmission by blood transfusion can be dangerous for the recipients considering their immunosuppressive status, underlying disease or other circumstances requiring blood transfusion. This argues in favour of testing all blood donations for HEV-3 to prevent transmission.


Assuntos
Doadores de Sangue , Hepatite E/prevenção & controle , Transfusão de Sangue , Genótipo , Hepatite E/transmissão , Hepatite E/virologia , Vírus da Hepatite E/genética , Vírus da Hepatite E/isolamento & purificação , Humanos , Hospedeiro Imunocomprometido , RNA Viral/sangue
13.
BMC Public Health ; 19(1): 685, 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31159757

RESUMO

BACKGROUND: Hepatitis G virus (HGV) infection transmitted from blood donors is a concern in China, as many articles about HGV infection in Chinese blood donors from different provinces have been published. This study aimed to evaluate the overall prevalence of HGV infection in Chinese blood donors and analyse the potential risk of HGV infection through blood transfusion in China. METHODS: We performed a literature search in PubMed, EMBASE, Web of Science, the Chinese BioMedical Literature Database (CBM) and the China National Knowledge Infrastructure (CNKI) up to October 2018 regarding the prevalence of HGV in Chinese blood donors. Eligibility assessment and data extraction were conducted independently by 2 researchers, and meta-analysis was performed to synthesize the data. Heterogeneity was evaluated using Cochran's Q test and quantified using the I2 statistic. Subgroup analyses were performed to identify the possible sources of heterogeneity. Publication bias was assessed using both funnel plot and Egger's tests. RESULTS: A total of 102 studies with 67,348 blood donors published from 1996 to 2016 and covering 26 provinces or municipalities were included for further analyses. The pooled prevalence of HGV was 3.91% (95%CI: 3.18-4.71%) by enzyme immune assay/enzyme linked immunosorbent assay (EIA/ELISA) and 3.25% (95%CI: 2.35-4.26%) by polymerase chain reaction (PCR). The prevalence of HGV may be significantly affected by region, province or municipality and potentially by the paid/voluntary status of the blood donors. No significant difference was found between plasma and full blood donation. CONCLUSIONS: The prevalence of HGV in blood donors from China was similar to that in blood donors from many other countries and higher than that of some other hepatitis viruses, such as hepatitis B virus. The risk of transfusion-transmitted HGV still exists after routine blood donor screening, especially in those patients coinfected with other hepatitis viruses and/or HIV. On the basis of our study, we may suggest adding HGV screening for blood transfusions in mainland China in the future.


Assuntos
Doadores de Sangue , Transfusão de Sangue , Vírus GB C , Hepatite Viral Humana/epidemiologia , Adulto , Doadores de Sangue/estatística & dados numéricos , China/epidemiologia , Ensaio de Imunoadsorção Enzimática , Feminino , Flaviviridae , Hepatite Viral Humana/virologia , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Prevalência , RNA Viral/sangue , Fatores de Risco , Adulto Jovem
14.
BMC Infect Dis ; 19(1): 525, 2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31200652

RESUMO

BACKGROUND: As technology progresses, several highly sensitive human immunodeficiency virus (HIV) screening kits are being researched and developed to quickly and efficiently identify serum HIV antibodies within the non-window period. In individuals who are HIV-seronegative, HIV infections that are not within a window period are rare. In such cases, all antibody detection methods will fail, and misdiagnosing these patients will have catastrophic consequences. CASE PRESENTATION: A 22-year-old male Chinese patient with diffuse exudative lesions in both lungs and initial symptoms of cough and dyspnoea was diagnosed with Pneumocystis jirovecii pneumonia (PJP) by aetiological examination, and the patient's plasma CD4+ T-cell count was extremely low. In China, PJP is prevalent in HIV-infected individuals. Pneumocystis jirovecii (P. jirovecii) has a high colonisation rate in patients with HIV infections. This patient was naturally suspected of being an HIV patient; however, serum HIV antibody tests were negative using both an enzyme-linked immunosorbent assay (ELISA) and a latex agglutination assay, and HIV was not detected by western blotting. Subsequently, the plasma HIV viral load was found to be extremely high on two repeated plasma HIV RNA tests, thus confirming HIV-seronegative acquired immunodeficiency syndrome (AIDS) in this patient. With administration of effective anti-P. jirovecii treatment and highly active antiretroviral therapy (HAART) after diagnosis, the patient's disease condition was rapidly controlled. CONCLUSION: This is the second reported case in China of an HIV-seronegative AIDS patient. Such cases are also rare worldwide. Although HIV-seronegative HIV infections are rare, AIDS should be considered in immunodeficient patients with opportunistic infections, even if the test results are HIV-seronegative. Plasma HIV RNA testing is important for such patients.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/sangue , Síndrome de Imunodeficiência Adquirida/sangue , Pneumonia por Pneumocystis/complicações , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/patologia , Infecções Oportunistas Relacionadas com a AIDS/virologia , Síndrome de Imunodeficiência Adquirida/complicações , Síndrome de Imunodeficiência Adquirida/patologia , Síndrome de Imunodeficiência Adquirida/virologia , Antibacterianos/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Humanos , Masculino , Pneumocystis carinii/isolamento & purificação , Pneumonia por Pneumocystis/sangue , Pneumonia por Pneumocystis/tratamento farmacológico , Pneumonia por Pneumocystis/patologia , RNA Viral/sangue , Resultado do Tratamento , Adulto Jovem
15.
Int J Infect Dis ; 85: 167-174, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31202908

RESUMO

OBJECTIVE: The nucleic acid-based polymerase chain reaction (PCR) assay is commonly applied to detect infection with Zika virus (ZIKV). However, the time- and labor-intensive sample pretreatment required to remove inhibitors that cause false-negative results in clinical samples is impractical for use in resource-limited areas. The aim was to develop a direct reverse-transcription quantitative PCR (dirRT-qPCR) assay for ZIKV diagnosis directly from clinical samples. METHODS: The combination of inhibitor-tolerant polymerases, polymerase enhancers, and dirRT-qPCR conditions was optimized for various clinical samples including blood and serum. Sensitivity was evaluated with standard DNA spiked in simulated samples. Specificity was evaluated using clinical specimens of other infections such as dengue virus and chikungunya virus. RESULTS: High specificity and sensitivity were achieved, and the limit of detection (LOD) of the assay was 9.5×101 ZIKV RNA copies/reaction. The on-site clinical diagnosis of ZIKV required a 5µl sample and the diagnosis could be completed within 2h. CONCLUSIONS: This robust dirRT-qPCR assay shows a high potential for point-of-care diagnosis, and the primer-probe combinations can also be extended for other viral detection. It realizes the goal of large-scale on-site screening for viral infections and could be used for early diagnosis and the prevention and control of viral outbreaks.


Assuntos
Reação em Cadeia da Polimerase Via Transcriptase Reversa , Infecção por Zika virus/diagnóstico , Zika virus/isolamento & purificação , Adulto , Criança , Feminino , Humanos , Limite de Detecção , Masculino , RNA Viral/análise , RNA Viral/sangue , Sensibilidade e Especificidade , Zika virus/genética
16.
BMC Vet Res ; 15(1): 202, 2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31200717

RESUMO

BACKGROUND: Bovine viral diarrhea virus (BVDV) infects various ungulates and causes reproductive failure in infected goats. BVDV has been detected among goats in the Republic of Korea, but the route of transmission remains unclear. Here, we aimed to investigate whether BVDV-1b circulating among Korean cattle can be transmitted to Korean native goats (Capra aegagrus hircus) and characterize the outcomes of BVDV infection in these goats. RESULTS: Four goats were inoculated intranasally with the Korean noncytopathic (ncp) BVDV-1b strain. Two goats exhibited clinical signs of illness, including coughing and nasal discharge. Nasal swabs and blood were collected to screen for viral RNA and BVDV antibodies. Using the 5'-untranslated region (UTR), viral RNA was detected in the nasal swabs of two goats (Goat 1 and 3) on 12 day post-inoculation (dpi) and in the blood sample of one goat (Goat 1) on 7 and 19 dpi. Using the N-terminal protease (Npro) region, viral RNA was detected in the blood sample of Goat 1 on 7 and 12 dpi. Antibodies to BVDV were detected in Goats 1 and 3 on 16-21 dpi using enzyme-linked immunosorbent assay. Sequence analysis of the virus from nasal swabs and blood samples, which was detected via RT-PCR, using the 5'-UTR and Npro regions led to the identification of the strain as ncp BVDV-1b and revealed changes in the nucleotide sequence of these goats. CONCLUSIONS: Our results indicate that changes in the nucleotide sequence are associated with the establishment of BVDV infection in Korean native goats; these changes may be owing to a process required for the establishment of infection in a new host reservoir. Broadly, these findings highlight the importance of BVDV surveillance in ungulates other than cattle.


Assuntos
Vírus da Diarreia Viral Bovina Tipo 1/genética , Doenças das Cabras/virologia , Infecções por Pestivirus/veterinária , Regiões 5' não Traduzidas , Animais , Anticorpos Antivirais/sangue , Vírus da Diarreia Viral Bovina Tipo 1/imunologia , Vírus da Diarreia Viral Bovina Tipo 1/patogenicidade , Ensaio de Imunoadsorção Enzimática/veterinária , Feminino , Doenças das Cabras/transmissão , Cabras , Mucosa Nasal/virologia , Infecções por Pestivirus/genética , Infecções por Pestivirus/virologia , RNA Viral/sangue , RNA Viral/genética , República da Coreia , Análise de Sequência de RNA
17.
Can J Vet Res ; 83(2): 110-121, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31097873

RESUMO

The efficacy of a porcine reproductive and respiratory syndrome (PRRS) subunit vaccine was evaluated and compared with a modified-live virus (MLV) vaccine under field conditions. Three farms were selected based on their history of respiratory diseases caused by co-infection with both PRRSV-1 and PRRSV-2. In each farm, 60 pigs were randomly allocated to 2 vaccinated and 1 unvaccinated groups (20 pigs per group). One group of pigs were administered the PRRS subunit vaccine at 21 and 42 days of age and another group administered the PRRS MLV vaccine at 21 days of age. The subunit vaccine had similar efficacy and, in some instances, performed even better than the MLV vaccine. Vaccination of pigs with either of the PRRS vaccines resulted in significantly improved growth performance in Farm B but not in Farm C. In Farm A, pigs vaccinated with the PRRS subunit vaccine had a better growth performance statistically compared to those vaccinated with the PRRS MLV vaccine. At the peak of PRRSV-1 and PRRSV-2 viremia, neutralizing antibodies and T-cell responses against PRRSV-1 and PRRSV-2 were at low levels suggesting that either vaccine is only able to provide a partial protection against co-circulating PRRSV-1 and PRRSV-2.


Assuntos
Síndrome Respiratória e Reprodutiva Suína/prevenção & controle , Vacinas Virais/imunologia , Animais , Anticorpos Antivirais/sangue , Interferon gama , Filogenia , Vírus da Síndrome Respiratória e Reprodutiva Suína , RNA Viral/sangue , RNA Viral/genética , Distribuição Aleatória , Suínos
18.
BMC Infect Dis ; 19(1): 476, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31138131

RESUMO

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is a newly identified severe infectious disease caused by SFTS phlebovirus (SFTSV). SFTS monitoring has been carried out since 2010 in mainland China. We analysed the detection results of SFTSV RNA and antibody in SFTS surveillance cases to provide basic data for SFTS diagnosis. METHODS: This study was conducted in Shandong Province. Sera of SFTS surveillance cases were collected to detect SFTSV RNA and antibody by real-time RT-PCR and enzyme-linked immunosorbent assay, respectively. Detection rates were calculated. SPSS 18.0 (Chicago, IL, USA) was used for statistical analysis to compare the detection rates of SFTSV RNA and antibodies among different sera groups. RESULTS: A total of 374 SFTS surveillance cases were enrolled. Overall, 93.3% (349/374) of the sera samples were collected within 2 weeks after onset, and 6.7% (25/374) were collected between 15 days and 45 days. Of these, 183 (48.9%) were positive for SFTSV RNA. The SFTSV RNA-positive rate peaked (52.2%) in samples collected ≤7 days after onset and then showed a decreasing trend. The detection rate of SFTSV-specific IgM antibody was 30.5% (46/151) and was highest in samples collected between 8 and 14 days (43.3%, 26/60). The positive rate of SFTSV-specific IgG antibody (17.9%, 27/151) showed an increasing trend with the specimen collection time. In total, 74.8% (113/151) of sera samples had the same SFTSV RNA and IgM antibody detection results. However, 23.2% (29/125) of SFTSV RNA-negative cases were IgM antibody-positive, and 8.6% (9/105) of IgM antibody-negative cases were SFTSV RNA-positive. CONCLUSIONS: SFTSV RNA detection was preferred for SFTSV infection during disease surveillance. For highly suspected SFTS cases, IgM antibody is suggested to make a comprehensive judgement.


Assuntos
Anticorpos Antivirais/sangue , Infecções por Bunyaviridae/epidemiologia , Infecções por Bunyaviridae/virologia , Phlebovirus/genética , RNA Viral/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , China/epidemiologia , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Febre/virologia , Humanos , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Phlebovirus/imunologia , Reação em Cadeia da Polimerase em Tempo Real , Trombocitopenia/epidemiologia , Trombocitopenia/virologia
19.
Ticks Tick Borne Dis ; 10(4): 868-874, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31047827

RESUMO

In Switzerland, tick-borne encephalitis (TBE) is a notifiable human disease with an average of 210 cases per year in the last 10 years (2008-2017). A national surveillance conducted in 2009 reported a prevalence of 0.46% for tick-borne encephalitis virus (TBEV) detected in ticks, which is in accordance with the prevalences found in Europe from 0.1%-5%. The Canton of Ticino in the southern part of Switzerland, geographically separated from the rest of the national territory by the Alps, is considered a non-endemic region, as no autochthonous clinical cases and no TBEV presence in ticks have ever been reported. In order to understand the epidemiological situation in Ticino, we conducted a large study investigating the TBEV presence in field-collected Ixodes ricinus ticks and in goat and human sera. Goats and sheep were considered as sentinel hosts showing persistence of antibodies also after 28 months in the absence of symptoms; this longevity supports the data validity to characterize an area with the TBEV status. The goat sera collection was composed of a total of 662 samples from 37 flocks. The total seroprevalence was 14.6%. 39 (40%) of the 97 SNT-positive samples showed an antibody titer ≥ 1:120 which indicates recent infection and consequently the probable presence of active foci among the pastures frequented by the goats belonging to 10 flocks. In total, 51 owners participated in the study and all were TBEV antibody-free. A total of 12'052 I. ricinus ticks (nymphs and adults) were collected and 1'371 pools were tested using quantitative real-time RT-PCR. Only one positive pool was reported with a prevalence of 0.35%. Metagenomic analysis revealed that the TBEV strain isolated from the ticks collected in Ticino is closely related to 2 strains coming from the Canton of Valais (99.1% and 98.7% identity, respectively), a neighbouring region of the Canton of Ticino. These two Cantons are close together but separated by high mountains (Alps) and we hypothesize that infected ticks were transported by wild animals from Valais into the Valle Maggia in Ticino where we found positive ticks. In conclusion, our data show for the first time the presence of TBEV in ticks and the related sero-reactivity in goats, confirming the presence of TBEV in the environment of the Canton of Ticino. Further surveillance studies will have to be conducted to follow the persistence of TBEV in this region.


Assuntos
Anticorpos Antivirais/sangue , Vírus da Encefalite Transmitidos por Carrapatos/isolamento & purificação , Encefalite Transmitida por Carrapatos/veterinária , Cabras/virologia , Ixodes/virologia , Infestações por Carrapato/veterinária , Animais , Vírus da Encefalite Transmitidos por Carrapatos/genética , Encefalite Transmitida por Carrapatos/epidemiologia , Cabras/parasitologia , Humanos , Metagenômica , Ninfa/virologia , Prevalência , RNA Viral/sangue , RNA Viral/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo Real , Estações do Ano , Análise de Sequência de DNA , Estudos Soroepidemiológicos , Suíça/epidemiologia , Infestações por Carrapato/epidemiologia
20.
Rev Soc Bras Med Trop ; 52: e20180465, 2019 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-31038622

RESUMO

INTRODUCTION: We evaluated the anti-hepatitis E virus (HEV) antibody prevalence and HEV-RNA in archived serum samples of non-A-C hepatitis, or suspected cases of HEV infection from the Eastern Brazilian Amazon from 1993 to 2014. METHODS: Serum samples (n = 318) were tested using ELISA and immunoblotting, and screened for HEV-RNA by RT-qPCR. RESULTS: Anti-HEV IgM and IgG were detected in 3.4% (11/318) and 5.9% (19/318) of the samples, respectively. All samples were HEV-RNA negative. CONCLUSIONS: HEV was detected at a low prevalence. Broader serological and molecular evaluation of HEV infection in the Amazon region should be carried out.


Assuntos
Anticorpos Anti-Hepatite/sangue , Vírus da Hepatite E/imunologia , Hepatite E/epidemiologia , Brasil , Ensaio de Imunoadsorção Enzimática , Feminino , Hepatite E/diagnóstico , Humanos , Immunoblotting , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Prevalência , RNA Viral/sangue , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Estudos Soroepidemiológicos
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